Preparation and Physicochemical Characterizations of p-Methoxycinnamic acid – Succinic Acid Cocrystal by Solvent Evaporation Technique

Abstract

Background: PMCA (p-Methoxycinnamic acid) is an active pharmaceutical ingredient derived from Kaempheria galanga L (known as kencur in Indonesia), which is poorly soluble in water. It can cause problems in the development of pharmaceutical dosage forms. Several methods have been carried out to increase the solubility of PMCA such as complex formation with β-cyclodextrin, or solid dispersion. The cocrystal formation method is a solubility enhancement method that has been developed recently.
 Aim: The aim of the study was the preparation and physicochemical characterization of PMCA co-crystal with succinic acid (SA) as its conformer by solvent evaporation technique.
 Methods: PMCA-SA cocrystal was made by the solvent evaporation method with a 1:1 molar ratio. Physicochemical characterization of PMCA and SA cocrystal was performed by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscope (SEM).
 Results: The DSC thermogram showed a decrease in the melting point of cocrystal compared to PMCA (173.55˚C), SA (187.55˚C), and its physical mixture (159.53˚C). The cocrystal thermogram displayed an endothermic peak at 158.46 ° C. Diffractogram of PMCA- SA cocrystal exhibited new diffraction peaks at an angle of 2θ = 21.92; 25.91 and 39.25˚ which was not found in the diffractogram of every single component nor its physical mixture. SEM photomicrograph showed PMCA-SA cocrystal as a rod-shaped crystal that had a different surface morphology and smaller size than the constituent materials.
 Conclusions: Based on the physicochemical characterization data above, it could be ascertained that PMCA-SA cocrystals had formed, these cocrystals were expected to increase the solubility of PMCA in water.